1,4-Dihydropyridine derivatives, such as nifedipine and nirvadipine, have calcium antagonism and, hence, are useful as a circulatory system drug such as a hypotensor and a vasodilator. However, their water solubility is insufficient so that it has been tried to convert them into inclusion compounds with cyclodextrin, i.e., forms with an increased water solubility, in order to impart them with pharmaceutical characteristics such as bioavailability and controlled release (Japanese Patent Application (Kokai) No. 6-100537).
It has also been tried to increase the water solubility of 1,4-dihydropyridine derivatives by introducing a basic tertiary amino group into themselves to form a medically acceptable salt.
For example, (4S)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid (3S)-3-(1-benzyl-3-pyrrolidinyl) ester 5-methyl ester (YM-09730) represented by the following formula ##STR2## [J. Med. Chem., 29, 2504 (1986)], (4S)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-diydropyridine-3,5-dicarboxylic acid 3-{2-[4-(4-benzhydryl-1-piperazinyl)phenyl]ethyl} ester 5-methyl ester represented by the following formula ##STR3## [Chem. Pharm. Bull., 39, 108 (1991)] and salts thereof are known to have calcium antagonistic activity as well as vasodilating activity and hypotensive activity, with these activities lasting [Arzneim. -Forsch./Drug Res. 38(11), 1666(1988), J. Med. Chem., 29, 2504 (1986), and Japanese Patent Publication (Kokoku) No. 57-30111]
However, only few 1,4-dihydropyridine derivatives have been known that themselves have electric charges and are imparted with, in a sense, permanent water solubility [J. Med. Chem., 3, 3743 (1993)].
Therefore, an object of the present invention is to provide optically active 1,4-dihydropyridine derivatives having themselves electric charges and permanently having water solubility.
Another object of the present invention is to provide a production method for producing such optically active 1,4-dihydropyridine derivatives.